The doctrine of specific etiology holds that a single agent is responsible for a single type of disease and a specific therapy can be used to treat that disease. This paradigm, which some trace back to the work of Louis Pasteur on infectious disease, raised awareness involving the factors contributing to a disease and inevitably led to the explosion in cell and molecular biology and the development of rational therapeutics. Yet, fundamental questions remain - Is a single factor necessary, or sufficient, for all diseases and to what extent do other factors play a role? In this regard there is a divergence between what can be learned from focus on a single molecule and what can be gleaned from examining the intact cell or tissue that secretes that molecule. Our coupling of the technology of tissue engineering with the cell biology, and the science of cardiomyopathy in particular in states of heightened stress, exposure to pheochromocytoma and pregnancy, may enable us to begin to answer some of these questions. The choice of our model system is based upon observations of the rapid onset and progression of cardiomyopathy in the peripartum state, and in particular in women who concomitantly are diagnosed with catecholamine-secreting pheochromocytoma tumors. To date the confluence of factors surrounding the onset and pathophysiology of this specific form of cardiomyopathy have received little attention. It remains unknown as to whether peripartum cardiomyopathy with pheochromocytoma develops solely due to increased levels of catecholamines or to an inter-play of pheochromocytoma- and pregnancy-related factors. Based on our observations we will specifically study the underlying mechanisms leading to the rapid onset of cardiomyopathies in pregnancy with or without concomitant pheochromocytoma. The proposed research project uses this specific model but seeks to understand broader questions. The findings may not only afford further appreciation of the pathophysiology and etiology of peripartum cardiomyopathy but also of general mechanisms in disease progression. [unreadable] [unreadable] [unreadable]